Efficacy of a new vacuum erection device (Vigor 2020) for erectile dysfunction: A retrospective study in Japan.

OBJECTIVES: The vacuum erection device (VED) is a second-line treatment tool recommended in erectile dysfunction (ED) guidelines but has long been unavailable in Japan. A new VED, Vigor 2020® (A & HB Company Limited, Tokyo, Japan), has now been manufactured and received medical approval from the Pharmaceuticals and Medical Devices Agency in Japan. We conducted a retrospective observational study of ED patients who used Vigor 2020 in clinical practice. METHODS: We analyzed male ED patients aged ≥20 years treated with Vigor 2020 in our outpatient clinics. The primary endpoint was improvement of erection as evaluated by an Erection Hardness Score (EHS) of ≥1 point. Secondary endpoints were improvement of sexual function and adverse events as evaluated by the International Index of Erectile Function (IIEF) and Male Sexual Health Questionnaire for assessing ejaculatory dysfunction (MSHQ-EjD). RESULTS: Thirty-three patients (mean age, 57.21 [27-86] years) could be evaluated before and after using Vigor 2020. Among the 16 patients with baseline EHS ≤2, 14 (93.33%) improved by ≥1 point, and 10 of these 16 patients (62.50%) improved to EHS ≥3 and could insert vaginally. Significant improvement was observed for IIEF total score and for the MSHQ-EjD in patients with an EHS of ≥3 after use of Vigor 2020. No patient experienced significant adverse events. CONCLUSIONS: The Vigor 2020 may be an efficacious treatment tool for ED. Patients with significant ED experienced not only significant improvement of erection but also improvement of ejaculation with its use.

Therapeutic efficacy and safety of a free-standing motorized ejaculation aid for patients with intravaginal ejaculatory dysfunction.

Purpose: There are no approved drugs or devices for the treatment of intravaginal ejaculation disorders, and treatment is often difficult. This study aimed to evaluate the efficacy and safety of the A10 Cyclone SA + PLUS® ejaculation aid (Rends Co., Ltd., Chiba, Japan), which allows the user to adjust the intensity of stimulation, for intravaginal ejaculation disorders. Methods: Each participant was instructed to perform practice masturbation with the A10 Cyclone SA + PLUS to simulate vaginal ejaculation. After 8 weeks of training, the participants were asked about their intravaginal ejaculation status. Sexual function was also evaluated before and after the training using several specific questionnaires, including the numerical rating scale for ejaculatory satisfaction. Results: Among the 10 participants (41.5 ± 3.21 years) who completed the training and questionnaire evaluation, four (40%) became capable of intravaginal ejaculation. The questionnaire evaluation showed predominant improvement after training in the ejaculation-capable group according to the numerical rating scale, which expresses satisfaction with ejaculation. The participants experienced no significant adverse events. Conclusion: As no effective treatment currently exists for intravaginal ejaculation disorders, we conclude that the A10 Cyclone SA + PLUS may be one treatment tool for intravaginal ejaculation disorders with good efficacy and no adverse events.

Evaluation of an Integrated Device Diagnostics Algorithm to Risk Stratify Heart Failure Patients　- Results From the SCAN-HF Study.

BACKGROUND: Integrated device diagnostics, Triage-HF, is useful in risk stratifying patients with heart failure (HF), but its performance for Japanese patients remains unknown. This is a prospective study of Japanese patients treated with a cardiac resynchronization therapy defibrillator (CRT-D), with a Medtronic OptiVol 2.0 feature.Methods and Results:A total of 320 CRT-D patients were enrolled from 2013 to 2017. All received HF treatment in the prior 12 months. Following enrollment, they were followed every 6 months for 48 months (mean, 22 months). Triage-HF-stratified patients at low, medium and high risk statuses at every 30-day period, and HF-related hospitalization occurring for the subsequent 30 days, were evaluated and repeated. The primary endpoint was to assess Triage-HF performance in predicting HF-related hospitalization risk. All device data were available for 279 of 320 patients (NYHA class II or III in 93%; mean left ventricular ejection fraction, 31%). During a total of 5,977 patient-month follow-ups, 89 HF-related hospitalization occurred in 72 patients. The unadjusted event numbers for Low, Medium and High statuses were 19 (0.7%), 42 (1.6%) and 28 (4.1%), respectively. Relative risk of Medium to Low status was 2.18 (95% CI 1.23-3.85) and 5.78 (95% CI 3.34-10.01) for High to Low status. Common contributing factors among the diagnostics included low activity, OptiVol threshold crossing, and elevated night heart rate. CONCLUSIONS: Triage-HF effectively stratified Japanese patients at risk of HF-related hospitalization.

Safety and efficacy of uninterrupted treatment with edoxaban or warfarin during the peri-procedural period of catheter ablation for atrial fibrillation.

BACKGROUND: The real-world safety and efficacy of uninterrupted anticoagulation treatment with edoxaban (EDX) or warfarin (WFR) during the peri-procedural period of catheter ablation (CA) for atrial fibrillation (AF) are yet to be investigated. METHODS: We conducted a two-center experience, observational study to retrospectively investigate consecutive patients who underwent CA for AF and received EDX or WFR. We examined the incidence of thromboembolic and bleeding complications during the peri-procedural period. RESULTS: The EDX and WFR groups included 153 and 103 patients, respectively (total: 256 patients). Demise or thromboembolic events did not occur in either of the groups. The incidence of major bleeding in the EDX and WFR groups was 0.7% and 2.9%, respectively. The total incidence of major/minor bleeding in the EDX and WFR groups was 7.8% and 8.7%, respectively. Of note, the incidence of bleeding complications in the uninterrupted WFR strategy group was markedly high in patients with an estimated glomerular filtration rate (eGFR) <30 (75%) or a HAS-BLED score ≥3 (60%). Patients with eGFR ≥30 and a HAS-BLED score ≤2 had a lower incidence of bleeding (<10%), regardless of the administered anticoagulation drug (EDX or WFR). CONCLUSIONS: This study confirmed the safety and efficacy of uninterrupted anticoagulation therapy using EDX or WFR in real-world patients undergoing CA for AF. Patients with severely impaired renal function and/or a higher bleeding risk during uninterrupted therapy with WFR were at a prominent risk of bleeding. Therefore, particular attention should be paid in the treatment of these patients.

Early efficacy of silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVES: To evaluate the early efficacy of the alpha(1A)-adrenoceptor selective drug, silodosin, for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia. METHODS: A total of 68 patients with an International Prostate Symptom Score (IPSS) of >==8 and a Quality of Life (QOL) index of >==2 were included. Changes in the IPSS and QOL index were evaluated before and after 1, 2, 3, 4, 5, 6, 7, 14, and 28 days of twice daily oral administration of 4 mg silodosin. Next, changes in IPSS subscores as well as voiding, storage, and post micturition symptoms were assessed. Changes in total IPSS based on symptom severity were also determined. RESULTS: Total IPSS and QOL index improved significantly from 19.38 +/- 7.46, 4.68 +/- 1.07 at baseline to 15.81 +/- 7.40, 4.22 +/- 1.30 at day 1. The subscores of voiding, storage, and post micturition symptoms were significantly decreased from 8.93 +/- 3.95, 7.97 +/- 3.88, and 2.49 +/- 1.70 at baseline to 7.28 +/- 4.09, 6.52 +/- 3.47, and 2.02 +/- 1.56 at day 1, respectively. This trend continued throughout the study. Regardless of severity, total IPSS were significantly decreased at day 1 and maintained throughout the study. CONCLUSIONS: Silodosin may be considered a promising treatment for benign prostatic hyperplasia/lower urinary tract symptom patients.

Study on the Effect of Irbesartan on Atrial Fibrillation Recurrence in Kumamoto: Atrial Fibrillation Suppression Trial (SILK study).

BACKGROUND: Experimental studies suggest that angiotensin II-receptor blockers can influence atrial remodeling and may prevent atrial fibrillation (AF). Therefore, we hypothesized that irbesartan may prevent the recurrence of AF following either catheter ablation or electrical cardioversion of AF. METHODS: Study on the Effect of Irbesartan on Atrial Fibrillation Recurrence in Kumamoto (SILK study) is a prospective, multicenter, randomized, and open-label comparative evaluation of the effects of irbesartan and amlodipine on AF recurrence in hypertensive patients with AF who are scheduled to undergo catheter ablation or electrical cardioversion of AF. The primary end point was either AF or atrial tachycardia (AT) recurrence. AF/AT recurrence was evaluated for 6 months using 24-h Holter electrocardiogram and portable electrocardiogram. The secondary endpoints included the change in blood pressure, the interval from the procedure to the first AF/AT recurrence, cardiovascular events, left atrial diameter (LAD), left ventricular ejection fraction (LVEF), and changes in the biomarkers [brain natriuretic polypeptide (BNP), high-sensitivity C-reactive protein (hs-CRP), urinary albumin/creatinine]. RESULTS: The study enrolled 98 patients (irbesartan; n=47, amlodipine; n=51). The recurrence of AF/AT was observed in 8 patients (17.0%) in the irbesartan group and in 10 patients (19.6%) in the amlodipine group. There was no significant difference in the AF/AT recurrence between the irbesartan and amlodipine groups. Blood pressure decreased similarly in both groups. There were no significant differences between the two groups as regards to the interval from the procedure to the first AF/AT recurrence, occurrence of cardiovascular events, changes in LAD and LVEF. BNP and urinary albumin/creatinine significantly decreased similarly in both groups, but no significant difference was found in hs-CRP between the two groups. CONCLUSIONS: In hypertensive patients with AF, treatment with irbesartan did not have any advantage over amlodipine in the reduction of AF/AT recurrence after catheter ablation or electrical cardioversion.

Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study.

INTRODUCTION: Phosphodiesterase type 5 inhibitors (PDE5i) are first-line therapy for most men with erectile dysfunction (ED). If ineffective, vacuum erection devices, intracavernous injections, and penile prosthesis implantation are suitable as second- or third-line therapies. However, very few patients select these therapies. It is critically important to improve erectile function with oral administration of effective agents. Administration of L-citrulline or transresveratrol in animal experiments has been reported to improve erectile function, but few such experiments have been performed on humans with ED. AIM: We aimed to investigate the efficacy of combination therapy of L-citrulline and transresveratrol in patients with ED despite their use of PDE5i. METHODS: In this randomized, double-blind, placebo-controlled crossover pilot study, men with ED (Sexual Health Inventory for Men [SHIM] score below 16) despite on-demand use of PDE5i received a placebo for 1 month or the active treatment (L-citrulline 800 mg/day and transresveratrol 300 mg/day) for another month. Patients continued on-demand use of PDE5i. MAIN OUTCOME MEASURE: The SHIM score, Erection Hardness Score (EHS), Aging Male Symptoms Scale-sexual domain (AMS-SD), and adverse events were examined. RESULTS: 20 patients ages 29-78 years were enrolled, and after 6 men withdrew, 13 concluded the study without adverse events. Mean SHIM score for the active treatment increased significantly (10.96 ± 1.21) compared with baseline (8.32 ± 1.21) and placebo (8.31 ± 1.23) (both P < .05). Mean EHS score for the active treatment (2.56 ± 0.26) also increased from baseline (2.31 ± 0.26), but not significantly (P = .79). Mean AMS-SD score was not significantly different in either group. CONCLUSION: To our knowledge, this is the first study to show that combination therapy of L-citrulline and transresveratrol is effective for ED treatment in men with added on-demand use of PDE5i. This combination supplement may be added if PDE5i is insufficient. Shirai M, Hiramatsu I, Aoki Y, et al. Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study. Sex Med 2018;6:291-296.

Comparison of uninterrupted anticoagulation with dabigatran etexilate or warfarin in the periprocedural period for atrial fibrillation catheter ablation: Results of the Japanese subgroup of the RE-CIRCUIT trial.

Background: There are limited data on uninterrupted anticoagulation with direct oral anticoagulants during catheter ablation for atrial fibrillation (AF), particularly in Japan. We planned a subgroup analysis of the RE-CIRCUIT study, comparing the use of uninterrupted dabigatran therapy with warfarin therapy during catheter ablation among the Japanese subgroup and with that in the total population. Methods: The RE-CIRCUIT study utilized a prospective, randomized, open-label, blinded endpoint design, and the primary endpoint was the incidence of major bleeding events (MBEs). Patients were randomized to uninterrupted dabigatran 150 mg twice daily or warfarin. In this study, we analyzed the results in Japanese patients. Results: Of 704 enrolled patients in the study, 112 Japanese patients were randomized to dabigatran (n = 65) or warfarin (n = 47). MBEs were experienced by two patients: one in the dabigatran group (1.6%, cardiac tamponade) and one in the warfarin group (2.2%, groin hematoma) (risk difference vs warfarin -0.6%; 95% CI -5.8, 4.7). Within the Japanese subgroup, there were no thromboembolic events in both groups. Conclusion: While not designed to show statistical difference between two treatment groups, our results from the Japanese subgroup supported those from the overall population. Furthermore, this study provided clinical information regarding MBE, especially cardiac tamponade, in Japanese patients.

The Pattern of Sexual Interest of Female-to-Male Transsexual Persons With Gender Identity Disorder Does Not Resemble That of Biological Men: An Eye-Tracking Study.

INTRODUCTION: Very little has been elucidated about sexual interest in female-to-male (FtM) transsexual persons. AIMS: To investigate the sexual interest of FtM transsexual persons vs that of men using an eye-tracking system. METHODS: The study included 15 men and 13 FtM transsexual subjects who viewed three sexual videos (clip 1: sexy clothed young woman kissing the region of the male genitals covered by underwear; clip 2: naked actor and actress kissing and touching each other; and clip 3: heterosexual intercourse between a naked actor and actress) in which several regions were designated for eye-gaze analysis in each frame. The designation of each region was not visible to the participants. MAIN OUTCOME MEASURES: Visual attention was measured across each designated region according to gaze duration. RESULTS: For clip 1, there was a statistically significant sex difference in the viewing pattern between men and FtM transsexual subjects. Longest gaze time was for the eyes of the actress in men, whereas it was for non-human regions in FtM transsexual subjects. For clip 2, there also was a statistically significant sex difference. Longest gaze time was for the face of the actress in men, whereas it was for non-human regions in FtM transsexual subjects, and there was a significant difference between regions with longest gaze time. The most apparent difference was in the gaze time for the body of the actor: the percentage of time spent gazing at the body of the actor was 8.35% in FtM transsexual subjects, whereas it was only 0.03% in men. For clip 3, there were no statistically significant differences in viewing patterns between men and FtM transsexual subjects, although longest gaze time was for the face of the actress in men, whereas it was for non-human regions in FtM transsexual subjects. CONCLUSION: We suggest that the characteristics of sexual interest of FtM transsexual persons are not the same as those of biological men. Tsujimura A, Kiuchi H, Soda T, et al. The Pattern of Sexual Interest of Female-to-Male Transsexual Persons With Gender Identity Disorder Does Not Resemble That of Biological Men: An Eye-Tracking Study. Sex Med 2017;5:e169-e174.

Effects of amiodarone on electrical and structural remodeling induced in a canine rapid pacing-induced persistent atrial fibrillation model.

Structural in addition to electrical remodeling may be induced by persistent atrial fibrillation per se and make atrial fibrillation refractory to antiarrhythmic drug therapy. Matrix metalloproteinases (MMPs) contribute to structural remodeling in the interstitial space. Amiodarone is effective in treating persistent atrial fibrillation compared with other antiarrhythmic drugs. In mongrel dogs, right atrial pacing at 540 beats/min (bpm) was performed along with ventricular pacing at 100 bpm for 6 weeks after atrioventricular node ablation. Right atrial pacing at 400 bpm was continued for 4 weeks with (n=5) or without (n=5) oral amiodarone (30 mg/kg/day). In sham dogs, only ventricular pacing was done with (n=4) or without (n=6) amiodarone. In atrial pacing without amiodarone group, electrical remodeling characterized by monophasic action potential duration shortening, loss of action potential duration-rate adaptation and depressed conduction velocity and structural remodeling characterized by slightly but significantly increased interstitial fibrosis and enhanced MMP-2 activity compared with sham group were observed, and sustained atrial fibrillation was easily induced. In atrial pacing with amiodarone group, both electrical and structural remodeling were reversed and sustained atrial fibrillation was not induced. In sham group with amiodarone, action potential duration prolongation and depressed conduction velocity compared with sham without amiodarone were observed, but either increased fibrosis or enhanced MMP-2 activity was not observed. Not only electrical but structural remodeling were induced in a canine persistent atrial fibrillation model. Amiodarone reversed both of them, which may be related to its high efficacy in preventing recurrence of persistent atrial fibrillation.

D-dimer level influences thromboembolic events in patients with atrial fibrillation.

BACKGROUND: Elevated coagulative molecular markers could reflect the prothrombotic state in the cardiovascular system of patients with non-valvular atrial fibrillation (NVAF). A prospective, cooperative study was conducted to determine whether levels of coagulative markers alone or in combination with clinical risk factors could predict subsequent thromboembolic events in patients with NVAF. METHODS: Coagulative markers of prothrombin fragment 1+2, D-dimer, platelet factor 4, and beta-thromboglobulin were determined at the enrollment in the prospective study. RESULTS: Of 509 patients with NVAF (mean age, 66.6 +/- 10.3 years), 263 patients were treated with warfarin (mean international normalized ratio, 1.86), and 163 patients, with antiplatelet drugs. During an average follow-up period of 2.0 years, 31 thromboembolic events occurred. Event-free survival was significantly better in patients with D-dimer level < 150 ng/ml than in those with D-dimer level>or==150 ng/ml. Other coagulative markers, however, did not predict thromboembolic events. Age (>or==75 years), cardiomyopathies, and prior stroke or transient ischemic attack were independent, clinical risk factors for thromboembolism. Thromboembolic risk in patients without the clinical risk factors was quite low (0.7%/year) when D-dimer was < 150 ng/ml, but not low (3.8%/year) when D-dimer was >or==150 ng/ml. It was >5%/year in patients with the risk factors regardless of D-dimer levels. This was also true when analyses were confined to patients treated with warfarin. CONCLUSIONS: D-dimer level in combination with clinical risk factors could effectively predict subsequent thromboembolic events in patients with NVAF even when treated with warfarin.

Mechanism of ST elevation and ventricular arrhythmias in an experimental Brugada syndrome model.

BACKGROUND: Although phase 2 reentry is said to be responsible for initiation of ventricular tachycardia (VT) in Brugada syndrome, information about the activation sequence during VT is limited. METHODS AND RESULTS: We developed an experimental Brugada syndrome model using a canine isolated right ventricular preparation cross-circulated with arterial blood of a supporter dog and examined the VT mechanism. Two plaque electrodes (35x30 mm) containing 96 bipolar electrodes were attached to the endocardium and epicardium. Saddleback and coved types of ST elevation in transmural ECG were induced by pilsicainide, a pure sodium channel blocker, and pinacidil, a KATP channel opener. Eighteen polymorphic VT episodes were recorded in 9 of the 12 preparations associated with ST elevation. Fourteen episodes spontaneously developed in 5 preparations after an extrasystole during basic drive pacing. Analysis of local recovery times revealed increased dispersion especially in epicardium, and the extrasystole originated from a site with a short recovery time, suggesting that phase 2 reentry was its mechanism. The other 4 VTs in 4 preparations were induced by premature stimulation. Analysis of the activation sequences during VT revealed reentry between epicardium and endocardium or reentry around an arc of a functional block confined to epicardium or endocardium with bystander activation of the other. CONCLUSIONS: Electrical heterogeneity in the recovery phase was induced in this experimental Brugada syndrome model, which can be a substrate for the development of phase 2 reentry and the subsequent reentry around an arc of the functional block, resulting in sustained VT.

Efficacy of a microwave antenna for ablation of the tricuspid valve--inferior vena cava isthmus in dogs as a treatment for type 1 atrial flutter.

INTRODUCTION: Radiofrequency catheter ablation of the tricuspid valve-inferior vena cava (TV-IVC) isthmus for treatment of atrial flutter (AFL), may in some cases require a large number of energy applications and a long procedure and fluoroscopy time. AIMS OF STUDY: Therefore, we studied the safety and efficacy of a 4 cm long microwave antenna mounted on a steerable 9Fr catheter for linear ablation of the TV-IVC isthmus. METHODS: In 6 anesthetized dogs, multi-electrode catheters were positioned in the coronary sinus (decapolar), at the His bundle (quadripolar) and around the TV annulus (decapolar) for pacing and recording atrial activation sequences before and after ablation. The microwave antenna was then positioned across the TV-IVC isthmus from the TV annulus (identified by equal A and V potentials) to the inferior vena cava with slight traction on the catheter to ensure adequate endocardial contact. Microwave energy was then applied at a fixed power for 120 seconds during each ablation attempt. Ablation was repeated until bi-directional isthmus block was demonstrated during pacing from the coronary sinus ostium and low lateral right atrium, respectively. RESULTS: Linear microwave ablation of the TV-IVC isthmus was completed in all ten dogs using a total of 2.6 +/- 1.17 energy applications per dog. Power was applied in a range of 45-50 watts. There were no acute procedural complications. Bi-directional TV-IVC isthmus block was achieved in all ten dogs, as demonstrated by a strictly descending activation wavefront in the ipsilateral atrial wall, during pacing from the CSO and LLRA respectively. In addition, after ablation conduction time to the LLRA during pacing from the CSO increased from 52 +/- 16.62 before to 87 +/- 12.74 msec (p <.05), and to the CSO during pacing from the LLRA from 51 +/- 12.43 before to 79.50 +/- 9.85 msec (p <.05). Gross and histological examination of the TV-IVC isthmus after ablation revealed continuous transmural lesions, ranging from 3-5 mm in width, spanning the entire TV-IVC isthmus in all ten dogs. CONCLUSIONS: (1) Microwave ablation of the TV-IVC isthmus was safe and effective in this study. (2) Ablation of the entire width and thickness of the TV-IVC isthmus can be rapidly achieved using a long microwave antenna in a fixed trans-isthmus position.

Effect of pilsicainide on dominant frequency in the right and left atria and pulmonary veins during atrial fibrillation: association with its atrial fibrillation terminating effect.

Dominant frequency reflects the peak cycle length of atrial fibrillation. In 34 patients with atrial fibrillation, bipolar electrograms were recorded from multiple atrial sites and pulmonary veins and the effect of pilsicainide, class Ic antiarrhythmic drug, on dominant frequency was examined. At baseline, mean dominant frequencies (Hz) in the right and left atria, coronary sinus and right and left superior pulmonary veins were 5.87 +/- 0.76, 6.08 +/- 0.60, 5.65 +/- 0.95, 6.12 +/- 0.88 and 6.59 +/- 0.89, respectively (P < 0.05, left superior pulmonary vein vs right atrium and coronary sinus). After pilsicainide (1.0 mg/kg/5 min), dominant frequency decreased at all sites in all patients. Atrial fibrillation was terminated at 5.9 +/- 2.2 min in 16 patients (Group A) with a decrease in the average of mean dominant frequencies at all sites from 5.80 +/- 0.72 to 3.57 +/- 0.63 Hz, was converted to atrial flutter at 7.3 +/- 1.4 min in 5 (Group B) with a decrease in the average dominant frequency from 5.83 +/- 0.48 to 3.08 +/- 0.19 Hz, and was not terminated in the other 13 (Group C) despite the average dominant frequency decrease from 6.59 +/- 0.76 to 4.42 +/- 0.52 Hz. In 14 of the 21 Groups A and B patients (67%), mean dominant frequencies at all recording sites were < 4.0 after pilsicainide, while they were < 4.0 in 1 of the 13 Group C patients (8%, P < 0.01). In conclusion, the degree of dominant frequency decrease by pilsicainide is closely related to its atrial fibrillation terminating effect: When dominant frequency in the atria decreases to < 4.0 Hz, atrial fibrillation is terminated with 93% positive and 63% negative predictive values.

Accumulation of risk factors enhances the prothrombotic state in atrial fibrillation.

BACKGROUND: The present study was conducted to investigate the relation between the accumulation of the risk factors of thromboembolism and the levels of hemostatic markers in patients with nonvalvular atrial fibrillation (NVAF). METHODS: Five hundred ninety-one NVAF patients and 129 control subjects were categorized into low, moderate or high risk of thromboembolism, according to CHADS(2) index. One point each was given to patients with advanced age (> or =75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with CHADS(2) score of 0, 1 or 2, and > or =3 were classified as low, moderate and high risk, respectively. Levels of hemostatic markers (platelet factor 4, beta-thromboglobulin, prothrombin fragment F1+2 and D-dimer) were determined. RESULTS: Of 591 patients with NVAF, 302 were treated with warfarin (mean international normalized ratio 1.88). D-dimer levels increased as the risk level increased irrespective of warfarin use. Particularly, NVAF patients without receiving warfarin (n=289) had significantly higher D-dimer levels than control patients (e.g., for high risk patients, 175+/-144 vs 75+/-87 ng/ml, p<0.001), while NVAF patients receiving warfarin had intermediate levels (136+/-156 ng/ml). F1+2 levels increased as the risk level increased, and were significantly suppressed by warfarin. Levels of markers of platelet activation (platelet factor 4 and beta-thromboglobulin) were increased in NVAF patients but not affected by the risk level. CONCLUSION: Coagulation and fibrinolytic activity is increased along with the accumulation of the risk factors of thromboembolism in NVAF patients.

Accumulation of risk factors increases risk of thromboembolic events in patients with nonvalvular atrial fibrillation.

BACKGROUND: Accumulation of risk factors could increase thromboembolic event rates in patients with nonvalvular atrial fibrillation (NVAF). To validate this hypothesis, a post hoc analysis was performed to determine the relationship of risk levels and thromboembolic events in patients with NVAF from our previous prospective study. METHODS AND RESULTS: Risk levels were quantified using the CHADS2 index in 509 patients with NVAF (66.3+/-10.3 years old). One point each was given for patients with advanced age (>or=75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with a CHADS2 score of 0 were classified as low risk, 1 to 2 a moderate risk and 3 or more were high risk. Because hypertrophic cardiomyopathy had emerged as an independent risk factor for thromboembolism, the original CHADS2 score was modified by adding 1 point to patients with hypertrophic cardiomyopathy. Warfarin was given to 263 patients (mean international normalized ratio (INR) at enrollment, 1.86), antiplatelets (aspirin or ticlopidine) to 163 patients and no antithrombotic therapy to 83. During a mean follow-up period of 2 years, 31 thromboembolic events occurred. As the risk level (modified CHADS2 score) increased, the event rate increased for both the patient groups receiving warfarin (p=0.035) and those not receiving warfarin (p=0.048). When a thromboembolic event occurred in patients who had been treated with warfarin, the mean INR level was 1.41. Twelve (75%) of 16 patients complicated with thromboembolism during warfarin treatment had INR levels below the optimal levels (1.6-2.6) for Japanese patients. CONCLUSION: Accumulation of risk factors could increase risk of thromboembolic events in patients with NVAF. Adherence to the guidelines for anticoagulation therapy is recommended.

Cardiac-directed expression of adenylyl cyclase VI facilitates atrioventricular nodal conduction.

OBJECTIVES: The purpose of this study was to test the hypothesis that cardiac-directed expression of adenylyl cyclase VI (AC(VI)) facilitates atrioventricular (AV) nodal conduction. BACKGROUND: Cardiac-directed expression of AC(VI), unlike other strategies to increase cyclic adenosine monophosphate generation, reduces mortality in murine cardiomyopathy. Recent reports suggest that AC(VI) expression may also protect against lethal bradycardia. METHODS: We performed immunofluorescence staining for AC(VI) in the AV node of transgenic mice. We then performed electrophysiologic studies (EPSs) using a 1.7-F octapolar catheter at the AV junction in 11 transgenic AC(VI) mice and 14 control mice. RESULTS: Immunofluorescence staining revealed increased AC(VI) expression in the AV node of transgenic mice versus controls. During EPS, AV intervals approximated PR intervals (R2 = 0.99) and related linearly to atrial-to-His intervals (R2 = 0.98; both p < 0.0001). Thus, we studied AV intervals to avoid electrocardiogram pacing artifacts and inconsistent inscription of His bundle electrograms. At baseline, AC(VI) mice had shorter AV intervals (47 +/- 9 ms) than controls (57 +/- 11 ms; p = 0.02), despite similar sinus rates. In pacing, AV intervals were shorter in AC(VI) mice than controls for a wide cycle-length range (p < 0.01). The AC(VI) mice also had shorter AV Wenckebach cycle lengths (AC(VI): 114 +/- 12 ms; control: 131 +/- 28 ms; p = 0.05) and ventriculo-atrial effective refractory periods (AC(VI): 97 +/- 21 ms; control: 127 +/- 15 ms; p = 0.05). We observed no differences between groups in sinus node function, and ventricular arrhythmias were not inducible. CONCLUSIONS: Cardiac-directed expression of AC(VI) facilitates AV nodal conduction without altering sinus node function. These results suggest the need to define a role for AC(VI) gene transfer in treating diseases of AV conduction.

Abnormal heart rate turbulence predicts the initiation of ventricular arrhythmias.

BACKGROUND: Abnormal heart rate turbulence (HRT) reflects autonomic derangements predicting all-cause mortality, yet has not been shown to predict ventricular arrhythmias in at-risk patients. We hypothesized that HRT at programmed ventricular stimulation (PVS) would predict arrhythmia initiation in patients with left ventricular dysfunction. METHODS: We studied 27 patients with coronary disease, left ventricular ejection fraction (LVEF) 26.7 +/- 9.1%, and plasma B-type natriuretic peptide (BNP) 461 +/- 561 pg/mL. Prior to arrhythmia induction at PVS, we measured sinus cycles after spontaneous or paced premature ventricular contractions (PVCs) for turbulence onset (TO; % cycle length change following PVC) and slope (TS; greatest slope of return to baseline cycle). T-wave alternans (TWA) was also measured during atrial pacing. RESULTS: At PVS, abnormal TO (> or =0%) predicted inducible ventricular tachycardia (VT; n = 10 patients; P < 0.05). TO was greater in inducible than in noninducible patients (2.3 +/- 3.1% vs -0.02 +/- 2.8%, P < 0.05) and correlated with LVEF (P < 0.05) but not with BNP. TS did not differ between groups. Conversely, ambulatory HRT differed significantly from HRT at PVS (TO -0.55 +/- 1.08% vs 0.85 +/- 3.02%, P < 0.05; TS 2.63 +/- 2.09 ms/RR vs 8.70 +/- 6.56 ms/RR, P < 0.01), and did not predict inducible VT but trended (P = 0.05) to predict sustained VT on 739 +/- 179 days follow-up. TWA predicted inducible (P < 0.05) and spontaneous (P = 0.0001) VT but did not co-migrate with HRT. CONCLUSIONS: Abnormal HRT measured at PVS predicted the induction of sustained ventricular arrhythmias in patients with ischemic cardiomyopathy. However, HRT at PVS did not correlate with ambulatory HRT, nor with TWA, both of which predicted spontaneous ventricular arrhythmias. Thus, HRT may reflect the influence of autonomic milieu on arrhythmic susceptibility and is likely complementary to traditional arrhythmic indices.

"V-H-A Pattern" as a criterion for the differential diagnosis of atypical AV nodal reentrant tachycardia from AV reciprocating tachycardia.

BACKGROUND: During ventricular extrastimulation, His bundle potential (H) following ventricular (V) and followed by atrial potentials (A), i.e., V-H-A, is observed in the His bundle electrogram when ventriculo-atrial (VA) conduction occurs via the normal conduction system. We examined the diagnostic value of V-H-A for atypical form of atrioventricular nodal reentrant tachycardia (AVNRT), which showed the earliest atrial activation site at the posterior paraseptal region during the tachycardia. METHODS: We prospectively examined the response of VA conduction to ventricular extrastimulation during basic drive pacing performed during sinus rhythm in 16 patients with atypical AVNRT masquerading atrioventricular reciprocating tachycardia (AVRT) utilizing a posterior paraseptal accessory pathway and 21 with AVRT utilizing a posterior paraseptal accessory pathway. Long RP' tachycardia with RP'/RR > 0.5 was excluded. The incidences of V-H-A and dual AV nodal physiology (DP) were compared between atypical AVNRT and AVRT. RESULTS: V-H-A was demonstrated in all the 16 patients (100%) in atypical AVNRT and in only 1 of the 21 (5%) in AVRT (P < 0.001). DP was demonstrated in 10 patients (63%) in atypical AVNRT and in 4 (19%) in AVRT (P < 0.05). The sensitivity of V-H-A for atypical AVNRT was higher than that of DP (P < 0.05). Positive and negative predictive values were 94% and 100%, respectively, for V-H-A and 71% and 74%, respectively, for DP. CONCLUSIONS: The appearance of V-H-A during ventricular extrastimulation is a simple criterion for differentiating atypical AVNRT masquerading AVRT from AVRT utilizing a posterior paraseptal accessory pathway.

Left ventricular outflow tract tachycardia originating from the right coronary cusp: identification of location of origin by endocardial noncontact activation mapping from the right ventricular outflow tract.

Idiopathic left ventricular outflow tract (LVOT) tachycardia has been shown to originate from a supravalvular site in some patients. Considerable attention recently has focused on identifying this variant of LVOT tachycardia on 12-lead ECG. We report the case of 15-year-old boy in whom a noncontact three-dimensional mapping electrode deployed in the right ventricular outflow tract (RVOT) assisted in identifying a supravalvular LVOT tachycardia. Observation of two early breakthrough sites in the RVOT and right ventricular septum suggested a right aortic cusp origin of the tachycardia. Pace mapping in the right aortic cusp identified a successful ablation site.